In a large number of chronic inflammatory disease states fibrosis (abnormal deposition of excess connective tissue) occurs in the vicinity of a cell mediated immune response, thus suggesting that immunocomponent cells are capable of secreting mediators which regulate fibroblasts. In search of such a mediator, studies were initially conducted to determine whether mixed lymphocyte reactions (MLR), an in vitro cell mediated immune response, generated fibroblast proliferation factors. Such factors were indeed found in MLR culture supernatants. Moreover, when analyzed by gel filtration chromatography and IEF, they were indistinguishable from a previously identified, macrophage-derived, thymocyte proliferation factor known as Interleukin 1 (IL 1). A second study examined the supernatants of human macrophages incubated with fibrogenic silica dust. This study showed that the fibroblast proliferation activity and Il 1 activity could not be resolved using gel filtration chromatography, size exclusion HPLC, IEF, ion exchange chromatography, or hydrophobic chromatography. In addition, the 2 activities were inactivated at the same rate at 56 degrees C and when treated with 4 different proteases having different substrate specificities. On the basis of these findings, studies have been initiated to define a specific, saturable receptor site for IL 1 on human dermal fibroblasts. In addition to further strengthening the evidence that IL 1 is capable of regulating nonlymphoid cells, the development of a radioreceptor assay would permit the measurement of IL 1 in pathological fluids. Efforts to date have been dedicated to the development of a rapid, efficient protocol for the purification of human IL 1 so that pure radioligand could be prepared. Thus far, Mug amounts of pure unlabeled IL 1 sufficient for detailed receptor studies have been obtained. Spectral analysis shows that the purified material is tryptophan rich while preliminary amino acid analysis suggests that the amino acid composition differs significantly from that published for murine IL 1. Future studies will be directed toward the isolation and functional/biochemical characterization of the IL 1 receptor.